Thinking Outside the Box: Utilizing Nontraditional Animal Models for COVID-19 Research

Round 1

Reviewer 1 Report

This is a well written paper with comprehensive and informative animal research data gathered from various research groups. Although there is no solid conclusion on the animal choices so far, its organization is neat and easy for readers to follow and hopefully suitable for scientists to take it as a summary/reference. I have minor comments for this manuscript. 

Comments:

1.) Line 106 - 108. The authors have pointed out the difference in age and physiology of the experimental animals and older patients. One point is some research groups did use old mice/laboratory animals to mimic such a condition. Authors may briefly comment on this issue to make it more inclusive. 

2.) Figure 2. The origin of the bat SARS-CoV-2 is still remain unknown. More bat viral surveillance studies from southern Asia have been published stating RaTG13 may probably not the ancestral viral strain of the human SARS-CoV-2 due to a much higher genomic similarity found in those newly discovered strains to the human strain. Moreover, the existence of furin cleavage site in SARS-CoV-2 is still questionable. I think the figure may need to modify to prevent premature assumption. 

3.) A recent outbreak in pet hamsters in Hong Kong have proven they can be naturally infected. Modify figure 2 accordingly. 

4.) Table 1 should include a column for human pathology for easier comparisons of those experimental animals with actual human infection.  

5.) Authors may briefly indicate which symptoms or cytokine fluctuations can resemble those in human in each sub-topic. 

 

Author Response

Please see attached file

Author Response File: Author Response.docx

Reviewer 2 Report

Review by Gunasekara S et al: Thinking outside the box: utilizing nontraditional animal models for COVID-19 research.

There are a few concerns that I listed below, but overall this short review is well written, timely, and provides a detailed overview that will be of interest to the SARS-CoV-2 research community and probably also to the general public.

1. Line 39f: Animal models are also critical to the development and test prophylactic treatments like vaccines.
2. Line 356f: The authors should include a paragraph that describes SARS-CoV-2 infection of hamsters other that Mesocricetus auratus – like Chinese hamsters, Roborovskis and other Phodopus hamsters – along with their strengths and limitations. Information on these (non-traditional) animal models are completely missing. Moreover, data on bushy tailed woodrats and deer mice should be at least mentioned in the manuscript text.
3. Line 405f: If do the authors mention HAdV- and NDV-based vaccines, why not include information on other preclinical vaccination trials in hamsters with promising vaccine candidates like 10.1073/pnas.2102775118 or 10.1016/j.celrep.2021.109493 for example?
4. Fig. 1: The authors use both “CoV” and “CoVs” to abbreviate coronaviruses (plural). And the + signs as well as “more”. Or “Virus” as well as “V.”. I think it would be good to keep these things consistent.
5. Fig. 2: Include references for panel A in the legend. Is it the mode of transmission you mean in line 139, or the mode of infection?
6. Tab. 1:
   1. Remove IG from legend, but include PO and OU
   2. Why do the authors only provide one inoculation dose, wouldn’t dose ranges make more sense here?

Author Response

Please see attached file

Author Response File: Author Response.docx